Organ-confined prostate cancer and the emergence of robotic prostatectomy.

   April 3, 2009   

Organ-confined prostate cancer and the emergence of robotic prostatectomy: What primary care physicians and geriatricians need to know.

John R. Carlucci, MD; Fatima Nabizada-Pace, MPH; David B. Samadi, MD

Prostate cancer is the fourth most common neoplasm worldwide, and the most common visceral neoplasm in the United States. With the advent of serum prostate-specific antigen (PSA) testing in the late 1980s and increasing awareness of men’s health issues, prostate cancer is a primary concern in the minds of many aging males. Though many men are living with prostate cancer (only about 16% of men diagnosed with prostate cancer ultimately die of it), it is important to remember that it is the cause of death in about 3% of the U.S. male population and the second-leading cause of death from cancer in men in the United States.1

Prostate cancer is the most common visceral neoplasm diagnosed in the United States and has gained ignificant public awareness over the past 20 years as a result of the serum prostatespecific antigen (PSA) screening test. Though there is potentially wide variability in presentation, most patients are diagnosed ith organ-confined disease. Treatments for localized prostate cancer include surgery, radiation, and active surveillance. One of the newer surgical modalities is roboticassisted laparoscopic prostatectomy, which has shown promise in improving cancer control and reducing the morbidity commonly associated with open radical prostatectomy. This article will discuss screening and treatment options for localized prostate cancer, with special focus on robotic prostatectomy and its advantages.
Carlucci JR, Nabizada-Pace F, Samadi DB.
Organ-confined prostate cancer and the emergence of robotic prostatectomy: What primary care physicians and geriatricians need to know.
Geriatrics. 2009;64(2):8-14.
Dr. Carlucci is a Fellow in the Division of Robotics and Minimally Invasive Surgery, Mount Sinai School of Medicine, New York City.
Ms. Nabizada-Pace is Program Manager, Division of Robotics and Minimally Invasive Surgery, Mount Sinai School of Medicine, New York City.
Dr. Samadi is Chief, Division of Robotics and Minimally Invasive Surgery, Mount Sinai School of Medicine, New York City.
Disclosure: The authors state that they have nothing to disclose.

Widespread screening with serum PSA and digital rectal examination (DRE) began in the late 1980s and has allowed earlier detection2,3. This has resulted in a stage migration such that 91% of cases are now being detected at a clinically localized stage and metastatic disease at the time of diagnosis is now rare in the United States1,4. However, screening for prostate cancer, as with many aspects of managing this disease, remains a controversial issue. Interpretation of serum PSA results is fraught with uncertainty but a better screening test has yet to be developed. Some of the inherent problems with interpreting PSA levels are that they fluctuate above and below normal levels over time even in healthy men, and that PSA usually increases as a man ages.

Age-specific PSA cut-offs have been devised which indicate acceptable PSA levels. For stable PSA values, the following age-specific guideline can be used: < 2.5 ng/mL for men up to age 49; < 3.5 ng/mL for men aged 50 to 59; < 4.0 ng/mL for men aged 60 and older. Current American Urological Association guidelines are that men over the age of 50 should be screened with DRE and serum PSA once a year; African-Americans and patients with a family history should begin at 40.

It now appears likely that PSA velocity (calculated over the course of at least 18 months) is more predictive of prostate cancer than the absolute PSA value. An abnormal PSA according to the above guidelines, a PSA velocity > 0.75ng/ml per year (even if the PSA remains below the age-specific cut-off), or an abnormal DRE warrants a urologic referral. The urologist performs a prostate biopsy under trans-rectal ultrasound guidance. If prostate cancer is found, further staging work-up may include CT scan of the abdomen/pelvis and a bone scan, depending on the aggressiveness and volume of cancer found on biopsy. A clinical stage can then be assigned based on these studies plus the biopsy findings, DRE, and PSA.

Robotic instruments allow flexibility, dexterity, and an even
greater range of motion than the human hand. Treatment
As discussed earlier, most patients are now diagnosed in the early stages of the disease, when the cancer is still organconfined. There are 3 major treatment options to consider: active surveillance, radiation, or surgery. (Metastatic disease, generally treated with androgen deprivation therapy and chemotherapy, is beyond the scope of this article.)

Active surveillance
According to some reports, 30% to 50% or more of prostate cancer cases in older men are overdiagnosed,5,6 meaning that these cancers would not have been detected without screening and would never cause harm to the patient. Because of this, patients with low-grade, low-stage disease and a life expectancy of less than 10 years may be offered an active surveillance protocol consisting of close monitoring with DRE and serum PSA every 3 to 6 months and prostate biopsy every 1 to 2 years.
Any evidence of disease progression warrants definitive treatment. This approach is still largely investigational when applied to younger men. It is important to keep in mind that treatment is more likely to be successful if it is given earlier while the tumor is smaller and the prospects for potency-sparing surgery are greater.

Radical prostatectomy
Surgery is considered the ‘gold standard’ for patients with organ-confined disease and greater than 10 years life expectancy. There are now several surgical approaches: perineal, open retropubic radical, laparoscopic radical, and robotic-assisted laparoscopic radical. The open retropubic approach dominated as the most common type of surgery for prostate cancer after the anatomic nerve-sparing technique was described by Walsh in the early 1980s and until the popularity of the robotic approach overtook it in the middle of this decade.
The 3 goals of successful radical prostatectomy in descending order of importance are cancer control (margins), urinary continence, and potency.

Why prostatectomy?
Following are important points regarding prostatectomy for both patients and physicians alike to keep in mind:

  • It is the only option that removes the entire prostate, whereas other options leave viable tissue and possible cancer behind.
  • Surgery is the only option that provides accurate staging, volume, tumor grade, and margins.
  • Rates of both upgrading (higher Gleason grade found on the final pathology than on biopsy) and upstaging (higher pathological stage than initial clinical stage) are approximately 30% each after prostatectomy; the true pathology would be otherwise unknown if radiotherapy was given. (Figure 1)
  • Follow-up is straightforward. PSA should be undetectable following a prostatectomy with negative surgical margins. PSA continues to be produced following radiation and is difficult to interpret.
  • There is no risk of a secondary iatrogenic malignancy developing after radiation.
  • Prostatectomy provides relief of any prior or future bladder outlet obstruction due to benign prostatic hyperplasia (BPH).
  • Radiation is still an option after surgery, whereas salvage prostatectomy after radiation remains a difficult and morbid operation.
  • Many patients benefit psychologically from knowing that the cancer is physically removed from the body.

Retropubic radical prostatectomy (RRP) was first reported by Millin in 19477. The surgery was associated with significant morbidity: high blood loss often requiring transfusion, incontinence, impotence, and a prolonged recovery. In the early 1980s Walsh described a new, more precise nerve-sparing technique of anatomical dissection that improved functional outcomes8. Schuessler performed the first laparoscopic radical prostatectomy (LRP) in 19919; the technique was later refined and popularized by Guilloneau10 and others11 in the late 1990s. It has since been demonstrated to be safe, effective, and similar to RRP in oncologic outcomes.

LRP provided the benefits of decreased blood loss (secondary to the increased abdominal pressure of the pneumoperitoneum and better visualization) and a minimally invasive approach but remained a technically challenging operation with a steep learning curve and poor ergonomics. Robotic-assisted laparoscopic prostatectomy (RALP) was first reported by Abbou et al12 in 2000.

It was popularized by Menon et al13 as a minimally invasive technique with vastly improved ergonomics and shorter learning curve relative to LRP. In particular, RALP offered 3-dimensional stereoscopic visualization and intuitive finger-controlled movements with range of motion surpassing that of the human hand. Robotic prostatectomy is now beginning to surpass both open and laparoscopic approaches in outcomes as robotic surgeons become more proficient.

Why the robotic approach?
The robotic approach has developed because there is still substantial room for improving important outcomes after open surgery. Urologists continue to seek ways to refine prostatectomy techniques. However, the robotic revolution is also patient-driven. Patients continue to seek out minimally invasive surgical approaches, hoping to minimize surgical trauma. Though robotic equipment is expensive, and a high surgery volume is necessary to make the purchase and maintenance of a robot cost-effective, the fact is, robotic prostatectomy is now by far the dominant surgical approach to prostate cancer, and its popularity continues to rise.

A learning curve of approximately 50 to 100 cases must be overcome before a level of efficiency can be obtained that will achieve financial viability. Furthermore, the importance of a dedicated, trained robotic OR team cannot be overemphasized. Steinberg et al14 examined the costs of overcoming the learning curves in 8 robotic prostatectomy series reported in the literature and concluded that RALP may be best suited to high volume prostatectomy centers.

Robotic vs. pure laparoscopy Surgeons who already have advanced laparoscopic skills may have no better results with the robot. That being said, the robot provides several advantages for most surgeons: more procedural control, better vision, greater wrist flexibility, suturing facility, instrument stability, and surgeon comfort.

Robotic vs. open Both laparoscopic approaches are considered less invasive than the traditional open prostatectomy. There are other considerations for RALP:

  • Though long-term oncologic efficacy data are as yet lacking for RALP, in series reported by experienced surgeons positive margin rates are usually improved compared to the open approach. For example, Smith et al15 noted a positive margin rate of 15% compared to a rate of 35% for the open approach. It should be noted, however, that patients in their open prostatectomy series had an overall higher risk profile (higher Gleason scores, PSA values, etc.), thereby possibly confounding the positive margin rates.
  • A common criticism of robotic surgery is that the lack of tactile feedback inherent to using the robot compromises the surgeon�s ability to judge whether cancer has breached the prostatic pseudocapsule and therefore diminishes cancer control. To counter this claim, many robotic surgeons point out that the superb visualization (11x magnification and 3-dimensional view) more than compensates for this, and in fact, the current literature demonstrates improved positive surgical margin rates for robotic series, as mentioned above.
  • With regards to postoperative complications, incidences are mostly similar, with the exception of a very low bladder neck contracture rate with the robot (<1%).
  • Many studies have reported less postoperative pain with the robotic approach.
  • Blood loss is unquestionably less. Farnham et al16 noted a 3% transfusion rate for open surgery and a <1% for robotic; also noted was a median discharge hematocrit of 33% vs. 38%, respectively. This is an especially important point when dealing with patients who refuse blood transfusions, such as Jehovah�s Witnesses. (Figure 2)
  • OR time has in most series been slightly longer for robotic, with more experienced robotic surgeons having shorter OR times. Our mean operative time is 127 minutes. (Figure 3)
  • Length of stay is typically less for robotic prostatectomy. Nelson et al17 reported a 95% rate of discharge after one hospital day vs. 82% for open surgery.
  • Continence: Smith et al demonstrated a faster return to continence in 3 months, but by 12 months the difference was less marked (94% vs. 97%).
  • Potency: Bilateral nerve-sparing radical prostatectomy is now the standard of care for localized disease with no evidence of extracapsular extension or frank involvement of the neurovascular bundles. Continued improvements in robotic technique, including eliminating the use of cautery during the dissection of the neurovascular bundles, have improved potency rates. Potency rates at one year are mostly in the range of 70% to 90%, though some have reported potency as high as 97%18-20, 13.
  • Though recent articles have pointed out lower satisfaction rates and higher regret amongst patients who have undergone RALP compared to open prostatectomy, authors have also pointed out that these findings may be due to inappropriate expectations of the new procedure21.

Radiation therapy
There are two main types of radiation therapy: external beam and brachytherapy (radioactive seed implantation). Delivery of external beam radiation continues to be refined to minimize surrounding tissue damage and maximize the radiation dose to the prostate. Intensity-modulated radiation therapy (IMRT) and proton radiation therapy are essentially variations on this theme, but their availability is currently somewhat limited due to cost and/or complexity.

With brachytherapy, radioactive seeds or needles are implanted directly into the prostate gland using ultrasound guidance to deliver a high dose of radiation to the tumor. Brachytherapy is relatively easy to perform and therefore has become popular for treatment of patients with clinically localized prostate cancer, but it is seldom used for the treatment of high-volume, high-risk prostate cancers. Urinary symptoms are more common after brachytherapy than after external beam radiotherapy, especially in patients with prostatic hyperplasia. Both treatments result in acute symptoms of proctitis or cystitis in approximately one third of patients; 5% to 10% develop permanent disorders related to bowel, bladder, and/or urethral function.

Approximately half of patients develop erectile dysfunction, depending on age andpreoperative erectile function. Patients with a high PSA level, high Gleason score, or large-volume tumor may benefit from androgen deprivation therapy in conjunction with radiotherapy or the combination of brachytherapy and external-beam radiation. It is important to note that there have been numerous studies documenting increased risk of secondary bladder and rectal malignancies after radiation for prostate cancer22-24, the most recent of which examined patients diagnosed and treated within the PSA era25.

Other treatments
Primary androgen deprivation therapy may be appropriate for older men, those with significant medical comorbidities precluding the use of curative therapy, or those who do not wish to undergo curative therapy. It is never curative, and remissions are not infrequent. Cryotherapy has been established as an appropriate and effective modality for recurrent, organ-confined prostate cancer after radiation26, though its role as a primary modality is still controversial and rates of erectile dysfunction following treatment remain high (up to 80%).

High-intensity focused ultrasound (HIFU), though gaining popularity, remains experimental and is currently not FDA-approved in the United States. Furthermore, the small studies done in Japan and Europe have very short follow-up. Stereotactic radiotherapy (Cyberknife ®) is being used atsome centers but is still investigational as efficacy data is lacking.

Follow-up after treatment for prostate cancert
Follow-up for patients who have received radiation therapy is difficult due to the fact that PSA usually does not decrease to undetectable levels and only reaches its nadir approximately 18 months after treatment has been given. There are guidelines set forth by the American Society for Therapeautic Radiology and Oncology but there is still substantial room for interpretation as to what constitutes an abnormal PSA after primary radiation therapy for prostate cancer.

In contrast, the patient who has had a robotic prostatectomy needs regular follow-up similar to any radical prostatectomy patient. Since the entiregland has been removed, follow-up PSA levels should be undetectable. An initial postoperative PSA should be obtained at 6 weeks after surgery. The patient should then be seen by his urologist at 3-month intervals for the first year, 6-month intervals for the second year, and annually thereafter. Each of these visits should include a DRE and a serum PSA as well as evaluation and treatment of functional outcomes such as continence and potency.

A PSA level above 0.2 ng/mL is considered elevated and warrants further evaluation and/or treatment by a urologist. Additional robotic prostatectomy information is available at author�s website:

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Organ-confined prostate cancer and the emergence of robotic prostatectomy.
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